Parathyroid hormone (PTH) has been proposed to be an important regulator of cardiovascular function in normotensive and hypertensive states. Acute administration of PTH causes relaxation of vascular smooth muscle resulting in vasodilation and hypotension. The mechanisms by which these actions occur are generally.unknown. In genetic hypertension, elevated circulating PTH levels and.depressed total and ionized serum calcium have been reported. The etiology of the calcium and PTH abnormalities in hypertension is also unknown. The main objective of this proposal is to determine the role of PTH as a vasodilator substance in the altered vascular responsiveness of hypertensive disease. The aorta and mesenteric vasculature of WKY and SHR will be examined for depressed relaxation responses to PTH. The mesenteric vasculature will also be studied to determine if PTH might enhance neuronally released norepinephrine via a presynaptic receptor mechanism similar to the presynaptic B2 receptor system. Altered vascular smooth muscle responsiveness to PTH will be studied to determine if the lesion resides at the level of the PTH receptor, adenylate cyclase or protein kinase. Also, the effects of PTH on calcium fluxes, intracellular ionized calcium concentrations and phosphatidylinositol will be examined in vascular tissue from nor- motensive and hypertensive rats. The development of hypertension, hyperparathyroidism, hypocalcemia and blunted target tissue responsiveness will be evaluated in longitudinal studies. Also, considering the recent interest in calcium metabolism and hypertension, studies of the effects of dietary calcium on the development of genetic hypertension and hyperparathyroidism will be performed. The results of these studies will provide basic information concerning the involvement of PTH in the biochemical processes which control blood vessel tone in physiological and pathological conditions.